October 19, 2012

2002 Meningitis Outbreak Offers Lessons In Treating New Cases

As the death toll from fungal meningitis continues to rise, a physician who spearheaded the 2002 meningitis outbreak demands that health experts take a look back at the lessons learned before venturing into unknown waters.

A new perspective paper has been published online in the Annals of Internal Medicine, detailing the lessons learned from treating patients who were affected by the 2002 outbreak of Exophiala dermatitidis meningitis due to contaminated, injectable coticosteroids prepared from a compounding pharmacy.

Dr. John R. Perfect, one of the health experts at the forefront of the 2002 outbreak, said in the article that the lessons he learned during the 2002 outbreak are applicable to the current outbreak, even though the 2012 infections are mainly from Exserohilum rostratum.

In 2002, the US Centers for Disease Control and Prevention (CDC) detailed 5 cases of E. (Wangiella) dermatitidis meningitis. Perfect said he was involved in the recognition and management of some of these patients. He said he and other experts learned, or so they thought, several important lessons from the outbreak.

Perhaps the most important lesson was that the compounding of preservative-free corticosteroids requires meticulous sterility to ensure lack of contamination. Without that level of sterility, fungi has the ability to grow aggressively and very rapidly. Also, once injected, the fungus can spread throughout human tissue fairly quickly, leading to invasive mycosis. He noted, however, they also learned that the incubation period for appearance of disease from the time of exposure can be up to 6 months. In the 2002 outbreak, many cases of those exposed were successfully treated because of low attack rate, resulting in only one fatality from fungal meningitis.

The reason the 2002 outbreak proved fearsome was predominantly due to patient worry and suffering. Combined with increased medical expenses, detailed public health surveillance, and a lack of trust in medications for fear of microbial contamination, the 2002 outbreak was a medical health crisis in the making.

While the 2012 cases are mainly tied to E. rostratum, the infections are occurring through the same process: injectable steroids produced in a compounding pharmacy. These injections were primarily given to older adults with low back pain and were probably administered as intra-articular injections.

As of October 19, there have been 20 reported deaths in the 2012 meningitis outbreak. What is making this year´s outbreak exponentially more worrisome is the fact that some 14,000 people have been exposed to the contamination. The New England Compounding Center (NECC), responsible for the contaminated injectable, had shipped some 17,000 of the contaminated steroid injections out to 76 medical facilities in 23 states as early as last May.

NECC, based in Framingham, Massachusetts, has now been shut down, and all products from the pharmaceutical have been secured and retained by the CDC and the FDA, which are currently in the midst of an aggressive investigation into the crisis.

The CDC has confirmed 4 new cases since Wednesday, with Virginia and Florida both reporting new deaths--overall cases in those states are now at 37 and 13, respectively. Michigan has so far seen 49 cases related to fungal meningitis this year, the most of any state. The CDC said the number of cases has jumped from 214 to 245 in just a few days.

While the FDA doesn´t regulate compounding facilities like they do regular pharmacies, it has flagged violations with at NECC as recently as 2006. The US House of Representatives´ investigative panel have given the FDA until October 31 to turn over all documents related to NECC, including communications with state regulators and the agency's commissioner, dating back to 2004.

The FDA had reportedly told the House last week it had been assured by NECC of the pharmacy´s compliance in 2007. However, the FDA investigators could not confirm whether the agency then took steps to ensure corrective measures had been taken.

An FDA spokesman said the agency had received the letter and would respond directly to the House panel.

“If the investigation finds any criminal misdoings, the Department of Justice must act decisively, file charges and prosecute the company or individuals responsible,” said US Representative Rosa DeLauro, a Connecticut Democrat who has proposed legislation to give FDA more authority to regulate compounding pharmacies.

This year´s meningitis outbreak will likely continue to get worse before it gets better. As the incubation period can take up to 6 months, it is likely most of the some 14,000 patients who had received the injectable have yet to encounter symptoms.

Cases of fungal meningitis had only first begun popping up last month when people began arriving at the ER of St. Thomas Hospital in Nashville, Tennessee with headaches, neck stiffness, nausea and other symptoms after having received epidural injections for back pain in a separate clinic at the hospital.

Because the product was shipped as early as last May, it could be November before an influx of cases begin pouring in. That is, of course, unless health officials can contact these patients who have received the injections, get them seen by medical professionals, and possibly get them on voriconazole treatments to stave off any infection.

Perfect said, based on the 2002 outbreak, voriconazole is the best possible antifungal drug for initial treatment. “Due to the aggressive and deadly nature of the disease, it is important for physicians to act decisively and early,” he said.

He warned that these outbreaks will continue to occur if pharmacy societies, the FDA, and the pharmaceutical industry do not work together to regulate pharmacy compounding.